{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:11:48Z","timestamp":1768450308607,"version":"3.49.0"},"reference-count":92,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Malaria continues to pose a significant public health threat, particularly across African nations, where <jats:italic>Plasmodium falciparum<\/jats:italic> accounts for over 90% of global malaria\u2010related deaths. The progression and survival of <jats:italic>P. falciparum<\/jats:italic> are heavily reliant on key proteins, including protein kinase 5 (PfPK5), which is essential for the parasite's cell division and survival. Due to its pivotal role, PfPK5 represents a promising target for antimalarial drug development. This study employed cheminformatics approaches to identify potential PfPK5 inhibitors derived from bioactive compounds in Nigerian plants with known antimalarial properties. A total of 196 compounds from 14 plant species were assessed for drug\u2010likeness, and the drug\u2010like candidates were docked into the active site of PfPK5. The binding free energies of the three top\u2010scoring compounds were subsequently evaluated alongside their pharmacokinetic and toxicological properties. Thirteen compounds demonstrated strong binding affinities, with docking scores ranging from \u22126.075 to \u221210.072\u00a0kcal\/mol, surpassing the performance of artemisinin, the reference drug, which showed a docking score of \u22125.613\u00a0kcal\/mol. Among these, marmesin, cryptolepinone, and lecanoric acid exhibited the most favorable interactions, with binding free energies of \u221248.73, \u221243.46, and \u221229.95\u00a0kcal\/mol, respectively, compared to \u221220.19\u00a0kcal\/mol for artemisinin. Molecular dynamics simulations over 100\u00a0ns confirmed the stability of these interactions. Furthermore, the identified compounds demonstrated favorable pharmacokinetic and safety profiles. In conclusion, this study identifies marmesin, cryptolepinone, and lecanoric acid as promising candidates for further computational and experimental investigations aimed at developing novel antimalarial therapies targeting PfPK5.<\/jats:p>","DOI":"10.1002\/cbdv.202402991","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:24:48Z","timestamp":1751397888000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Plant\u2010Derived Natural Products Against <i>Plasmodium falciparum<\/i> Malaria Causative Agent by Targeting Protein Kinase 5: Insights Into Computational Approaches"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9804","authenticated-orcid":false,"given":"Haruna Isiyaku","family":"Umar","sequence":"first","affiliation":[{"name":"Department of Biochemistry Federal University of Technology Akure Nigeria"},{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soukayna","family":"Baammi","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory College of Computing Mohammed VI Polytechnic University Ben Guerir Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix Oluwasegun","family":"Ishabiyi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Ibadan Ibadan Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullahi Tunde","family":"Aborode","sequence":"additional","affiliation":[{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"},{"name":"Department of Chemistry Mississippi State University USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omoboyede","family":"Victor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Federal University of Technology Akure Nigeria"},{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blessing O.","family":"Awoyemi","sequence":"additional","affiliation":[{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"},{"name":"Department of Microbiology Federal University of Technology Akure Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibukun Faith","family":"Michael","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Federal University of Technology Akure Nigeria"},{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bashir Bolaji","family":"Tiamiyu","sequence":"additional","affiliation":[{"name":"Department of Plant Biology University of Ilorin Ilorin Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim Akindeji","family":"Makinde","sequence":"additional","affiliation":[{"name":"Computer\u2010Aided Therapeutic Discovery and Design Laboratory Akure Nigeria"},{"name":"Department of Information Systems School of Computing (SOC) Federal University of Technology Akure Akure Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chibuzo Carole","family":"Nweze","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Natural and Applied Sciences Nasarawa State University Keffi Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Bourhia","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology and Natural Resources Valorization Faculty of Sciences Ibn Zohr University Agadir Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pravin","family":"Badhe","sequence":"additional","affiliation":[{"name":"Swalife Biotech Ltd Unit 3D North Point House North Point Business Park Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7492-4428","authenticated-orcid":false,"given":"Soufyane","family":"Lafraxo","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agri\u2010Food and Health Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University Fez Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gamal A.","family":"Shazly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, King Saud University  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.891573"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.48327\/mtsi.v3i2.2023.375"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40101\u2010020\u201000251\u20109"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44197\u2010024\u201000228\u20102"},{"key":"e_1_2_12_6_1","first-page":"225","volume-title":"Advances in Protein Chemistry and Structural Biology","author":"Cassiano G. C.","year":"2021"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116145"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2003.09.020"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00605\u201017"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800625"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010018\u20100911\u20109"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2021.1962291"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4538602"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e05562"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.734263"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20109199\u2010JVATITD\u20102022\u20100079"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc\u20102019\u20100307"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3897\/folmed.61.e47965"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.9734\/ijbcrr\/2020\/v29i830208"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169\u2010409X(00)00129\u20100"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000292e"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0492002"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2196699"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2015.1032936"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894\u2010020\u201004495\u20101"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct900549r"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21816"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2020.105660"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894\u2010022\u201005373\u20108"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2019.0323"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2021.0069"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106774"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25020321"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0717\u201097072021000205164"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747\u20100285.2010.01075.x"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17020144"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathmechdis\u2010012419\u2010032640"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908\u2010023\u201000805\u20109"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2022.104130"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S265602"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S279433"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.18231\/j.ijcaap.2022.003"},{"key":"e_1_2_12_45_1","unstructured":"J. D.Chirawurah I. C.Ezenyi D.Sahal andE.Al \u201cMarmesin Isolated FromCeltis durandiiEngl. Root Bioactive Fraction Inhibits \u03b2\u2010Hematin Formation and Contributes to Antiplasmodial Activity \u201d (2023) http:\/\/ugspace.ug.edu.gh:8080\/handle\/123456789\/39553."},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116804"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3026370"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112734"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2024.125336"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/horticulturae9060705"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2020.11.009"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1049\/nbt2.12018"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105280"},{"key":"e_1_2_12_54_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/978-3-030-84860-6","volume-title":"ADME Encyclopedia","author":"Talevi A.","year":"2022"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182312836"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.54844\/cai.2022.0077"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113113"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2022.147937"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13111779"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2020.103962"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2020.122052"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43188\u2010020\u201000056\u2010z"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312808"},{"key":"e_1_2_12_64_1","volume-title":"StatPearls","author":"Hallare J.","year":"2024"},{"key":"e_1_2_12_65_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/B978-0-12-820007-0.00012-X","volume-title":"Remington","author":"Overholser B. R.","year":"2021"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112290"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2019.10.010"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.137168"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics9070152"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0018516"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-6815-2_7"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr9010071"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c00057"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822\u2010019\u201000267\u2010z"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.0c01326"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC05230C"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2022.118901"},{"key":"e_1_2_12_78_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-030-94651-7_7","volume-title":"Transdisciplinarity","author":"Badar M. S.","year":"2022"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmb.21512"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119264"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imu.2022.100880"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822\u2010018\u20100120\u20103"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1177\/13596535231199838"},{"key":"e_1_2_12_84_1","first-page":"181","volume-title":"Advances in Protein Chemistry and Structural Biology","author":"Sneha P.","year":"2016"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176208"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1209\/0295\u20105075\/133\/36003"},{"key":"e_1_2_12_87_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/AABC.S476404","article-title":"Employing Hexahydroquinolines as Pf CDPK4 Inhibitors to Combat Malaria Transmission: An Advanced Computational Approach","volume":"17","author":"Oduselu G. O.","year":"2024","journal-title":"Advances and Applications in Bioinformatics and Chemistry"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.3c00354"},{"key":"e_1_2_12_89_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/9781394182862.ch27","volume-title":"Polypharmacology: Strategies for Multi\u2010Target Drug Discovery","author":"Coulson L. B.","year":"2025"},{"key":"e_1_2_12_90_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2024.111362","article-title":"Study of the Naturally Occurring Lignan Brachangobinan A as Antiplasmodial Agent: Synthesis, Biological Evaluation, and In Silico Prediction","volume":"406","author":"Ariefta N. R.","year":"2024","journal-title":"Chemico\u2010Biological Interactions"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.4c00054"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.11.001"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.08.004"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202402991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:24:53Z","timestamp":1751397893000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202402991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":92,"alternative-id":["10.1002\/cbdv.202402991"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202402991","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02991"}}